Microscopic histopathology of single and sequential controlled cortical impact (CCI) and closed head injury (CHI). (A) Representative photomicrographs of hematoxylin and eosin staining at 6 h after CHI, CCI, or CCI-CHI showing acute cellular injury (argyrophilic cells) in left hemispheric hippocampus of CCI and CCI-CHI mice but not CHI. In contrast, no acute cellular injury/death was observed in right hemispheric hippocampus (dentate gyrus shown in all micrographs) of CCI or CHI, but degenerative cells were noted in right dentate gyrus of sequential injury mice. Inset, representative example of propidium iodide labeling of right sided dentate gyrus cells 6 h after CCI-CHI 83 g. (B) Amyloid precursor protein (APP) immunohistochemistry showing robust axonal injury in left hemispheric corpus callosum after CCI and CCI-CHI but not CHI. Only occasional APP-positive axons were detected in right hemispheres in each group. Scale bar, 100 μm.